PharmExperts.com

Diana Woodruff-Pak (Temple University, Philadelphia, PA) used cholesterol-fed rabbits as a model of AD for evaluation of currently available and potential anti-Alzheimer drugs. These animals developed typical Alzheimer pathology, including behavioral changes and deposition of ß-amyloid and even tau. Galantamine and donepezil partially protected animals from Alzheimer symptomatology.

S. Waxman, MD, PhD. - Medical need for new analgesics is discussed by S. Waxman (Yale University) who evaluated the role of selective subtypes of sodium channels, particularly 1.7 and 1.8 subtypes, in the perception of pain. There is an unmet medical need for drugs to treat chronic pain and inhibitors of selective sodium channels are in development as novel analgesics.

Dr. Michael Spedding published recently a review on the role of cytokines and neurotrophins in disease. Neurotrophins (e.g. BDNF) have beneficial effects on neuronal plasticity and brain metabolism. Inflammatory cytokines (e.g. IL1beta)oppose the effects of neurotrophins. Both, neurotrophins and cytokines are targets for the development of new drugs affecting central nervous system. Brain-derived neurotrophic factor (BDNF) is the main activity-dependent neurotrophic factor. Interleukin 1beta...

Michael Spedding (Institute Internatinales Servier, Paris, France) described how neuroprotection can be achieved by either by blockade or by stimulation of AMPA (a-amino-3-hydroxy-5-methyl-4-isoxazole propionic acid) receptors. Low threshold AMPA receptor stimulation leads to the release of BDNF (brain-derived neurotrophic factor) which is neuroprotective. Blockade of AMPA receptors reduces excitotoxicity leading to neuroprotection. BDNF is a major activity-dependent neurotrophic factor...

Michael Rogawski (University of California, Davis) summarizes his research on the antiepileptic activity of neurosteroids (e.g. ganaxolone, allopregnanolone). They are allosteric modulators of GABAA receptors and are active in many models of epilepsy. They are expected, however, to be most effective in catamenial epilepsy, infantile spasms or adult partial seizures. National Institutes of Health (NIH) is currently sponsoring a clinical trial of progesterone (precursor of allopregnanolone)...

R.A. Flavell (Yale University, New Haven, CT) discusses the role of Transforming Growth Factor ß (TGFß) in disease. In the central nervous system of a murine model of AD this cytokine appears to prevent macrophages from attacking ß-amyloid. Flavell visualizes that selective blockade of this TGFß activity could lead to the destruction of plaques in patients with AD.

Dr. Remi Quirion (McGill University, Montreal, Quebec, Canada) described enhancement of the effects of pain-related peptides by PGE2 . This finding suggests a new, possible complimentary approach to the therapy of pain. Qurion also discussed anti-Alzheimer effect of polyphenols. This effect appears to be due not due to their antioxidant activity only. Quirion suggested the existence of membrane protein than binds polyphenols.

Daniele Piomelli, PhD. - Another approach was discussed by D. Piomelli (University of California, Irvine). URB 597, an inhibitor of fatty acid amide hydrolase (FAAH), is expected to increase anandamide signaling and is being currently clinically tested in the therapy of pain. An increase in anandamide signaling may also be useful in the therapy of depression. This is a novel approach to the development of antidepressants. The signaling can be enhanced by blocking anadamide metabolism or by...

J. Kocsis, PhD. - The current approaches to the therapy of multiple sclerosis are reviewed by J. Kocsis (Yale University). His research emphasizes remyelination as an approach to the therapy of multiple sclerosis and spinal cord injury.

Z. Khachaturian, PhD. - New approaches to the therapy of Alzheimer’s disease (AD) are discussed in video interviews of this series. According to Z. Khachaturian (Potomac, MD) substantial progress has been made during the last 10 years in our understanding of pathogenesis of Alzheimer’s disease as well as in the discovery of biomarkers and therapeutic approaches. In addition to cholinergic drugs, inhibitors of plaque formation have been discovered, but the currently available...